Available information indicates that antibody mechanisms initiate most experimental and human glomerulonephritis. Much less is known about the immune mechanisms, humoral or cellular, responsible for tubulointerstitial nephritis (TIN). Even with the information available and the use of aggressive therapeutic maneuvers to modulate nephritogenic antibody responses, damage often progresses relentlessly to renal failure necessitating costly and only partially satisfactory measures such as dialysis. Studies herein will quantitate the humoral and cellular mechanisms leading to initiation, evolution, progression, and/or regression of immunologically-induced autoimmune models of TIN in the rat using nephritogenic anti-tubular basement membrane (TBM) antibodies and effector T cell lines and clones. Assessment of the contributions of antibody and immune cells and their clones will be defined during the evolutionary stages of sequential antibody deposition, polymorphonuclear leukocyte accumulation, and subsequent lymphocyte and monocyte/macrophage dominated stages of TIN in the Brown Norway (BN) rat induced with heterologous TBM in adjuvants. A new model of cell-mediated and transferrable nodular TIN produced in the Lewis (LEW) rat by immunization with BN renal basement membrane (RBM) will be studied using similar techniques for comparison to the antibody related BN TIN. The factors controlling the nephritogenic autoimmune responses including their induction and modulation will be elucidated. These studies entail modulation of cell surface receptors and study of the mechanisms of induction of disease resistance using attenuated T cell lines. It will be necessary to identify the antigens reactive with the humoral and cellular immune elements involved. The LEW rat, with proper immunization, develops anti-basement membrane antibodies similar to those seen in human Goodpasture's syndrome. This serious human disease is currently lacking a model to examine the poorly understood immunopathogenesis of the not infrequent episodic and sometimes fatal pulmonary hemorrhage of these patients. The immunized LEW rat will be explored as a potential model for detailed investigation of the pathogenesis of this immunologically-induced lung injury.